Interpreting Coagulation Results Flashcards
What needs to be interpreted in coagulation studies
The clinical situation
-A bleeding patient
=Is it a congenital bleeding disorder? i.e. A primary coagulation problem
=Is it bleeding secondary to another pathology? i.e. A secondary coagulation problem
-An asymptomatic patient
=Have you picked up an undiagnosed congenital bleeding disorder?
=Is it a lupus anticoagulant? (this will be explained later)
-Clotting abnormalities that are not necessarily causing bleeding but secondary to other pathologies
=Liver disease/DIC not causing bleeding
The actual results
-APTT
-PT
-Fibrinogen
APTT
-Intrinsic
PT
-Extrinsic
-Tissue factor to factor 7
Fibrin clot
-Common pathway (intrinsic and extrinsic)
-10
-2: prothrombin to thrombin to fibrinogen to fibrin
Rules of coagulation cascade
-The only cause of an isolated raised PT is a low F7
-Common pathway: 2 x 5 = 10
What are the factors?
-I = Fibrinogen – no longer referred to as Factor I
-II = Factor II/Prothrombin/thrombin
-III = Tissue factor – absence of this is lethal so it was dropped as it didn’t represent a disease state
-IV = Calcium (not a coagulation protein)
-V = Factor V
-VI = In the original experiments it was discovered this was the active form of Factor V so it was dropped
-VII/VIII/IX/X/XI/XII = All true coagulation factors
Coagulation Screen
-Activated Partial Thromboplastin Time (APTT)
-Prothrombin Time (PT)
-Fibrinogen
What is included in bleeding history?
-Mode of delivery – Ventouse/forceps – excess bruising
-IM vitamin K – haematoma
-Guthrie test – prolonged bleeding
-Umbilical cord – prolonged bleeding, prolonged healing
-Immunisations – haematoma
-Teething – excess bleeding
-Falls/dental work/surgery
-Menstruation
Describe a 50:50 correction in prolonged APTT in isolation
-If the APTT is raised in ISOLATION check that a 50:50 correction has been done
-If the APTT is prolonged this should always be on the results available to you
-What is a 50:50 correction?
-All factors are considered normal if they are 50% (0.5iu/dL) or more
-All APTT reagents are calibrated to give a normal result if the factor levels are 50% or more
-A correction is when the patient’s serum is mixed with an equal volume of normal serum then the APTT is repeated
-Even if the patient’s serum has 0% of any of the factors they will be brought up to 50% at least by the addition of normal serum
-Therefore a normal APTT ‘should’ be seen
What is the APTT doesn’t correct back to normal? Prolonged in isolation
-If the prolonged APTT normalises then the implication is that a low factor level has been corrected by the normal serum and a low factor level is present in the patient
-Not normal:
-This implies something is inhibiting the test and preventing normalisation
-Otherwise known as an inhibitor (also heparin contamination will cause this always check from where the sample was drawn eg. A heparinised line)
-What is an inhibitor?
-An inhibitor is an antibody that is either;
=Factor specific (eg. An anti-FVIII antibody) or;
=A non-specific antibody that generally binds to phospholipid membranes –frequently termed a lupus anticoagulant: Usually not pathogenic, Apart from in anti-phospholipid syndrome
How does the inhibitor cause the non-correction of the APTT after normal serum has been added?
-A factor specific antibody
=Knocks out the factor in the incoming normal serum
=Keeps the APTT prolonged because the total level (patient+ normal serum factor) is <50%
-A non-specific antibody to phospholipid
=It will bind to the phospholipid that is part of the APTT reagent
=Inhibits its ability to stimulate clotting and keeps the APTT prolonged
Who gets inhibitors for prolonged APTT?
-Non-specific anti-phospholipid antibodies termed ‘lupus anticoagulants’ are VERY frequent in febrile illness especially in children – non-clinical issue
-Anti-phospholipid antibodies can uncommonly occur as part of SLE
-Specific anti-factor antibodies (inhibitors) can occur in haemophilia as some patient’s immune systems interpret the recombinant treatment factor as foreign
-Can occur in adults with no factor deficiency - acquired haemophilia (50% idiopathic, 50% secondary to malignancy or rheumatological disorders)
=Converts the previously normal adult into a moderate to severe haemophiliac
Why the name Lupus Anticoagulation?
- The ‘lupus’ bit– These non-specific antibodies against phospholipid occur either transiently as part of an inter-current infection/inflammatory state or as part of the Anti-Phospholipid Syndrome which is most frequently secondary to lupus!
- The ‘anticoagulant’ bit– Because it prolongs the APTT (though doesn’t cause bleeding this is a laboratory phenomenon)
What happens if the APTT completely corrects?
-Consider intrinsic factor testing
-Consider a von Willebrand screen
=VWF is a carrier protein for F8. If there is anything wrong with VWF then it will impact the F8 level and prolong the APTT
Further investigations of prolonged APTT
-Asymptomatic patient
=Do nothing and re-test in 12 weeks – by far and away the most common reason is a lupus anticoagulant – non-clinical and transient
=Consider a lupus screen – this will hit 2 birds with 1 stone– It picks up non-clinical lupus anticoagulants and also the pathogenic anti-phospholipid antibodies seen in SLE + antiphospholipid syndrome
-In a bleeding patient
=Specialised tests to pick up acquired haemophilia can be doneby the haematologists
